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腺苷在体外可减缓犬心肌的缺血代谢:与缺血预处理的关系。

Adenosine slows ischaemic metabolism in canine myocardium in vitro: relationship to ischaemic preconditioning.

作者信息

Vander Heide R S, Reimer K A, Jennings R B

机构信息

Department of Pathology, Duke University Medical Center, Durham, NC 27710.

出版信息

Cardiovasc Res. 1993 Apr;27(4):669-73. doi: 10.1093/cvr/27.4.669.

DOI:10.1093/cvr/27.4.669
PMID:8324803
Abstract

OBJECTIVE

Studies in rabbits suggest that the cardioprotective effects of adenosine against lethal cell injury may be related to production of adenosine and subsequent activation of adenosine A1 receptors. However, it is not known whether intracoronary adenosine therapy can mimic the metabolic sparing effects of preconditioning in rabbits or dogs. The purpose of this study was to determine the effect of intracoronary adenosine on ischaemic metabolism in totally ischaemic canine myocardium.

METHODS

Dog hearts (n = 13) were excised and the coronary arteries were perfused with an oxygenated Krebs' buffer containing glucose. Adenosine was added to the buffer perfusing the circumflex (treated) region. Following perfusion, control and treated beds from each heart were subjected to 90 min total ischaemia at 37 degrees C. Tissue levels of ATP and glycolytic intermediates were determined at several time points during the ischaemic incubation.

RESULTS

Adenosine significantly slowed the rate of ATP depletion, glycogen utilisation, and lactate accumulation during the first 20 minutes of total ischaemia.

CONCLUSIONS

The results suggest that adenosine is capable of slowing ischaemic metabolism and they are consistent with the hypothesis that adenosine may mediate ischaemic preconditioning.

摘要

目的

对兔子的研究表明,腺苷对致死性细胞损伤的心脏保护作用可能与腺苷的产生及随后腺苷A1受体的激活有关。然而,冠状动脉内腺苷治疗是否能模拟兔子或狗预处理的代谢节省效应尚不清楚。本研究的目的是确定冠状动脉内腺苷对完全缺血犬心肌缺血代谢的影响。

方法

切除犬心脏(n = 13),用含葡萄糖的含氧 Krebs 缓冲液灌注冠状动脉。将腺苷添加到灌注回旋支(处理)区域的缓冲液中。灌注后,将每颗心脏的对照和处理区域在37℃下进行90分钟的完全缺血。在缺血孵育期间的几个时间点测定组织中ATP和糖酵解中间产物的水平。

结果

在完全缺血的前20分钟内,腺苷显著减慢了ATP消耗、糖原利用和乳酸积累的速率。

结论

结果表明腺苷能够减缓缺血代谢,这与腺苷可能介导缺血预处理的假说一致。

相似文献

1
Adenosine slows ischaemic metabolism in canine myocardium in vitro: relationship to ischaemic preconditioning.腺苷在体外可减缓犬心肌的缺血代谢:与缺血预处理的关系。
Cardiovasc Res. 1993 Apr;27(4):669-73. doi: 10.1093/cvr/27.4.669.
2
Attenuation of postischaemic dysfunction by ischaemic preconditioning is not mediated by adenosine in the isolated rat heart.在离体大鼠心脏中,缺血预处理对缺血后功能障碍的减轻作用并非由腺苷介导。
Cardiovasc Res. 1993 Aug;27(8):1522-30. doi: 10.1093/cvr/27.8.1522.
3
Improved functional recovery by ischaemic preconditioning is not mediated by adenosine in the globally ischaemic isolated rat heart.在全脑缺血的离体大鼠心脏中,缺血预处理所带来的功能恢复改善并非由腺苷介导。
Cardiovasc Res. 1993 Apr;27(4):663-8. doi: 10.1093/cvr/27.4.663.
4
The effect of body temperature on myocardial protection conferred by ischaemic preconditioning or the selective adenosine A1 receptor agonist GR79236, in an anaesthetized rabbit model of myocardial ischaemia and reperfusion.在麻醉兔心肌缺血再灌注模型中,体温对缺血预处理或选择性腺苷A1受体激动剂GR79236所赋予的心肌保护作用的影响。
Br J Pharmacol. 1999 Sep;128(2):385-95. doi: 10.1038/sj.bjp.0702799.
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Kinetic analysis of 99mTc-sestamibi evaluates the protective effects by ischaemic preconditioning on ischaemic myocardium in an isolated rabbit heart.99mTc-司他米比的动力学分析评估了缺血预处理对离体兔心脏缺血心肌的保护作用。
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Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart.有证据表明,腺苷A3受体可能介导了预处理对离体兔心脏所提供的保护作用。
Cardiovasc Res. 1994 Jul;28(7):1057-61. doi: 10.1093/cvr/28.7.1057.
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Adenosine receptor blockade enhance glycolysis in hypoperfused guinea-pig myocardium.
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Manipulations in glycogen metabolism and the failure to influence infarct size in the ischaemic rabbit heart.
Eur J Anaesthesiol. 2002 Jul;19(7):495-503. doi: 10.1017/s0265021502000819.
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Acadesine extends the window of protection afforded by ischaemic preconditioning in conscious rabbits.阿卡地新可延长清醒家兔缺血预处理所提供的保护时限。
Cardiovasc Res. 1995 May;29(5):653-7.
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Ischaemic preconditioning is not dependent on neutrophils or glycolytic substrate at reperfusion in rabbit heart.
Cardiovasc Res. 1992 Dec;26(12):1195-8. doi: 10.1093/cvr/26.12.1195.

引用本文的文献

1
Reductions in mitochondrial O(2) consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium.慢性冬眠心肌在模拟缺血后线粒体氧消耗减少及高能磷酸水平的维持
Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H223-32. doi: 10.1152/ajpheart.00992.2008. Epub 2009 Apr 24.
2
Biochemical dysfunction in heart mitochondria exposed to ischaemia and reperfusion.暴露于缺血再灌注的心脏线粒体中的生化功能障碍。
Biochem J. 2005 Sep 1;390(Pt 2):377-94. doi: 10.1042/BJ20042006.
3
Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury.
腺苷代谢与转运选择性抑制剂的差异性心脏保护作用:嘌呤释放在缺血及再灌注损伤中的作用
Mol Cell Biochem. 1998 Mar;180(1-2):179-91.
4
Suppression of the degradation of adenine nucleotides during ischemia may not be a sufficient mechanism for infarct size limitation by preconditioning.在缺血期间抑制腺嘌呤核苷酸的降解可能不是预处理限制梗死面积的充分机制。
Basic Res Cardiol. 1996 Nov-Dec;91(6):425-32. doi: 10.1007/BF00788723.
5
Loss of glycogen during preconditioning is not a prerequisite for protection of the rabbit heart.预处理期间糖原的丢失并非兔心脏获得保护的必要条件。
Basic Res Cardiol. 1996 Sep-Oct;91(5):374-81. doi: 10.1007/BF00788717.
6
Involvement of ATP-sensitive potassium channels in preconditioning protection.ATP敏感性钾通道在预处理保护中的作用。
Basic Res Cardiol. 1994 Nov-Dec;89(6):563-76. doi: 10.1007/BF00794956.
7
Attenuation of the antiarrhythmic effects of ischaemic preconditioning by blockade of bradykinin B2 receptors.通过阻断缓激肽B2受体减弱缺血预处理的抗心律失常作用。
Br J Pharmacol. 1994 Dec;113(4):1167-72. doi: 10.1111/j.1476-5381.1994.tb17120.x.